Through an integrated program of basic and clinical studies, we shall continue to examine the effects of opiates and amphetamines on catecholamine metabolism, and to explore the role of catecholamines in the reinforcing properties of these drugs and the pathophysiology of opiate and amphetamine addiction. The basic studies include: 1) studies of the effects of acute and chronic administration of morphine and d- or 1-amphetamine on levels of 3-methoxy-4-hydroxyphenylglycol sulfate--MHPG-SO4, in rat brain regions; 2) studies of effects of morphine and amphetamines on thresholds of intracranial reinforcement and locomotor activity; 3) studies to determine whether the morphine-inducted increase in MHPG sulfate levels in rat brain can be conditioned. While we have obtained preliminary findings suggesting that we can condition this morphine-induced biochemical effect, further studies including additional control groups will be necessary to confirm and extend these initial findings. Through these neuropharmacological studies we hope to be able to explore possible relationships among the neurochemical, physiological and behavioral effects of opiates and amphetamines. In our clinical studies, we shall continue to examine the effects of heroin on urniary catecholamines and metabolites in an attempt to confirm and extend previous findings. Towards this end we are continuing to perform clinical studies following the protocol which included a 10-day drug-free period, 2 days of naltrexone or placebo (administered on a double-blind basis), 10 days of heroin availability for self-administration (while of double-blind naltrexone or placebo) and 5 days of methadone administration to subjects who were not receiving naltrexone. These biochemical data will be used to explore the possible relationships between changes in catecholamine metabolism and various physiological and behavioral variables including drug seeking behavior.